Effects of intrathecal opioids use in cesarean section on breastfeeding and newborns’ weight gaining

Objective: To assess the association between intrapartum intrathecal opioid use and breastfeeding and weight gain following cesarean section. Materials and methods: The prospective double-blinded study was conducted on term pregnant women, undergoing elective cesarean section under spinal anesthesia. They divided into two groups. In the first group, intrathecal Morphine was used to achieve analgesia during or after the operation. The remainder divided into two subgroups, those who did not receive any opioid or those received systemic opioids. Following labor breastfeeding accessed in a follow-up, two month latter. Results: There was no difference between the demographic variables of the mothers and newborns APGAR score and weight at the time of birth. Breastfeeding rate was similar in intrathecal group in compare with other patents (P value = 0.518). While, the infants’ weight at the end of second month was lower in spinal opioid group (P value = 0.036). Conclusion: The present study was the first to suggest that spinal (intrathecal) opioids do not have any impact on breastfeeding. However the relationship between spinal anesthesia on weight gaining needs more investigation

Mas-related G-protein–coupled receptors inhibit pathological pain in mice

An important objective of pain research is to identify novel drug targets for the treatment of pathological persistent pain states, such as inflammatory and neuropathic pain. Mas-related G-protein–coupled receptors (Mrgprs) represent a large family of orphan receptors specifically expressed in small-diameter nociceptive primary sensory neurons. To determine the roles of Mrgprs in persistent pathological pain states, we exploited a mouse line in which a chromosomal locus spanning 12 Mrgpr genes was deleted (KO). Initial studies indicated that these KO mice show prolonged mechanical- and thermal-pain hypersensitivity after hind-paw inflammation compared with wild-type littermates. Here, we show that this mutation also enhances the windup response of dorsal-horn wide dynamic-range neurons, an electrophysiological model for the triggering of central pain sensitization. Deletion of the Mrgpr cluster also blocked the analgesic effect of intrathecally applied bovine adrenal medulla peptide 8–22 (BAM 8–22), an MrgprC11 agonist, on both inflammatory heat hyperalgesia and neuropathic mechanical allodynia. Spinal application of bovine adrenal medulla peptide 8–22 also significantly attenuated windup in wild-type mice, an effect eliminated in KO mice. These data suggest that members of the Mrgpr family, in particular MrgprC11, may constitute an endogenous inhibitory mechanism for regulating persistent pain in mice. Agonists for these receptors may, therefore, represent a class of antihyperalgesics for treating persistent pain with minimal side effects because of the highly specific expression of their targets

Current evidence for treatment with nusinersen for spinal muscular atrophy : a systematic review

Recent discovery of nusinersen, an antisense oligonucleotide drug, has provided encouragement for improving treatment of spinal muscular atrophy. No therapeutic options currently exist for this autosomal recessive motor neuron disorder. Nusinersen is developed for intrathecal use and binds to a specific sequence within the survival motor neuron 2 pre-messenger RNA, modifying the splicing process to promote expression of full-length survival motor neuron protein. We performed a MEDLINE and CENTRAL search to investigate the current evidence for treatment with nusinersen in patients with spinal muscular atrophy. Four papers were withheld, including two phase-3 randomized controlled trials, one phase-2 open-label clinical trial and one phase-1 open-label clinical trial. Outcome measures concerned improvement in motor function and milestones, as well as event-free survival and survival. Results of these trials are hopeful with significant and clinically meaningful improvement due to treatment with intrathecal nusinersen in patients with early- and later-onset spinal muscular atrophy, although this does not restore age-appropriate function. Intrathecal nusinersen has acceptable safety and tolerability. Further trials regarding long-term effects and safety aspects as well as trials including broader spinal muscular atrophy and age categories are required and ongoing

Intraspinal Drug Delivery Reservoir Refill Procedure by Non-Physician Clinicians: A Nation-Wide Survey of Training, Pocket Fill Experience, and Life-Long Learning Behaviors

Intraspinal drug delivery (IDD) is a safe and efficacious method used to deliver medications for the treatment of chronic neurologic disease that requires periodic reservoir refills that can place patients at risk for a rare, accidental but potentially life-threatening, pocket fill. In the United States (US), non-physician clinicians perform this procedure. This study reports the results of a nationwide survey completed by 65 non-physician clinicians, obtained through social media, who performed the reservoir refill procedure. The results of the survey showed no standardized training was used, lack of attention to existing clinical practice guidelines in the training given, lack of supervision and mentoring for inexperienced clinicians, an unexpected number of pocket fills, and limited participation in professional meetings where intraspinal therapy is discussed. Suggestions for improvement are given

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value

Antinociceptive Effects of Intrathecal Landiolol Injection in a Rat Formalin Pain Model

Perioperative beta-blocker administration has recently been recommended for patients undergoing cardiac or other surgery due to the beneficial cardiovascular effects of these agents. In addition, some studies have reported that perioperatively administered beta-blockers also have analgesic effects. In this study, to investigate the antinociceptive effects and the analgesic profile of landiolol, we examined the effects of intrathecal landiolol administration on nociceptive pain behavior and c-fos mRNA expression (a neural marker of pain) in the spinal cord using a rat formalin model. We found that pain-related behavior was inhibited by intrathecal landiolol administration. Moreover, the increase in c-fos mRNA expression on the formalin-injected side was less pronounced in rats administered landiolol than in saline administered controls. Thus, intrathecal administration of landiolol exhibited antinociceptive effects. Further investigation of the antinociceptive mechanism of landiolol is required

BU10038 as a safe opioid analgesic with fewer side-effects after systemic and intrathecal administration in primates

© 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.Background: The marked increase in mis-use of prescription opioids has greatly affected our society. One potential solution is to develop improved analgesics which have agonist action at both mu opioid peptide (MOP) and nociceptin/orphanin FQ peptide (NOP) receptors. BU10038 is a recently identified bifunctional MOP/NOP partial agonist. The aim of this study was to determine the functional profile of systemic or spinal delivery of BU10038 in primates after acute and chronic administration. Methods: A series of behavioural and physiological assays have been established specifically to reflect the therapeutic (analgesia) and side-effects (abuse potential, respiratory depression, itch, physical dependence, and tolerance) of opioid analgesics in rhesus monkeys. Results: After systemic administration, BU10038 (0.001–0.01 mg kg −1 ) dose-dependently produced long-lasting antinociceptive and antihypersensitive effects. Unlike the MOP agonist oxycodone, BU10038 lacked reinforcing effects (i.e. little or no abuse liability), and BU10038 did not compromise the physiological functions of primates including respiration, cardiovascular activities, and body temperature at antinociceptive doses and a 10–30-fold higher dose (0.01–0.1 mg kg −1 ). After intrathecal administration, BU10038 (3 μg) exerted morphine-comparable antinociception and antihypersensitivity without itch scratching responses. Unlike morphine, BU10038 did not cause the development of physical dependence and tolerance after repeated and chronic administration. Conclusions: These in vivo findings demonstrate the translational potential of bifunctional MOP/NOP receptor agonists such as BU10038 as a safe, non-addictive analgesic with fewer side-effects in primates. This study strongly supports that bifunctional MOP/NOP agonists may provide improved analgesics and an alternative solution for the ongoing prescription opioid crisis.Peer reviewedFinal Published versio

Optimum imaging and diagnosis of cerebrospinal fluid rhinorrhoea

Imaging is an important component in the investigation of unilateral watery rhinorrhoea suspicious of cerebrospinal fluid (CSF). Whilst the demonstration of the presence of beta 2 transferrin confirms that CSF is present it may prove difficult to demonstrate the exact site of origin. Fine detail coronal computed tomography (CT) with sections of 1-2 mm thickness through the anterior skull base may show small dehiscences and fractures. The commonest site for congenital dehiscences is the cribriform niche adjacent to the vertical attachment of the middle turbinate anteriorly and the superior and lateral walls of the sphenoid posteriorly. In the presence of frequent or constant CSF rhinorrhoea a CT cisternogram can be helpful in defining the exact site of the leak. Magnetic resonance imaging (MRI) is reserved for defining the nature of soft tissue Le. inflammatory tissue, meningoencephalocele or tumour. Finally, per-operative intrathecal fluorescein is helpful when imaging does not prove positive. A management algorithm for CSF rhinorrhoea is presented

Transient neurologic symptoms following spinal anesthesia with isobaric mepivacaine: A decade of experience at Toronto Western Hospital

Background: Transient neurologic symptoms (TNSs) can be distressing for patients and providers following uneventful spinal anesthesia. Spinal mepivacaine may be less commonly associated with TNS than lidocaine; however, reported rates of TNS with intrathecal mepivacaine vary considerably. Materials and Methods: We conducted a retrospective cohort study reviewing the internal medical records of surgical patients who underwent mepivacaine spinal anesthesia at Toronto Western Hospital over the last decade to determine the rate of TNS. We defined TNS as new onset back pain that radiated to the buttocks or legs bilaterally. Results: We found one documented occurrence of TNS among a total of 679 mepivacaine spinal anesthetics (0.14%; CI: 0.02–1.04%) that were performed in 654 patients. Conclusion: Our retrospective data suggest that the rate of TNS associated with mepivacaine spinal anesthesia is lower than that previously reported in the literature